Analysis of human fetal skin by immunofluorescent techniques identified sequential antigen development of laminin, bullous pemphigoid antigen, pemphigus antigen and anchoring fibril antigen identified by monoclonal antibodies AF-1 and AF-2. Additional monoclonal antibodies were generated from mice immunized with human fetal skin. Specific monoclonal antibodies generated reacted with cytokeratins of human epidermis, human fetal periderm and basement membrane zone. Improved techniques of separating human fetal epidermis from dermis have allowed mice to be immunized with earlier human fetal tissues in an effort to develop monoclonal antibodies to very early antigens of development. In the future, specific characterization of currently developed monoclonal antibodies will require more intense biochemical analysis with two dimensional gel techniques and immunoprecipitation. Development of new monoclonal antibodies will result from mice immunized with human fetal epidermal tissues obtained before 12 weeks gestational age. Further development of current in vitro and in vivo (transplanted to nude mice) fetal keratinocyte culture systems may allow the generated monoclonal antibodies to act as probes of molecular control and response during fetal development. In addition these monoclonal antibodies will be used to continue evaluation of differentiating benign and malignant epidermal neoplasms and genetic disorders.